Most common among synthetic vascular constructs are vascular grafts. However, there has been a steady increase in the development of some allied constructs such as vascular wraps, patches, and endovascular stent grafts. Most of the design criteria used in the development of useful vascular grafts are usually applicable for other forms of vascular constructs in spite of noticeable differences in end-use requirements. Since the use of Vinyon N cloth (made of a copolymer of vinyl chloride and acrylonitrile) by Voorhees and coworkers in 1952, as a tubular construct for bridging arterial defects, many investigations have been directed toward the development of synthetic vascular grafts. Of the many systems investigated, Polyethylene terephthalate (PET) and polytetrafluoroethylene (PTFE) are the most commonly used polymers. Needless to say, limited attention was given to vascular patches or wraps, which can be made from similar materials as those of the vascular grafts, but which are used less frequently than the grafts.
Although PTFE and PET vascular grafts, having a diameter of more than 6 mm, have been clinically successful, development of clinically acceptable, small diameter grafts has been generally unsuccessful. Thrombus and neointima formation will readily occlude the small diameter synthetic vascular grafts. The resulting loss of patency remains the greatest obstacle to the development of a small caliber vascular prosthesis. Thus, there is a need for an engineered material that will provide the necessary mechanical and thromboresistant properties for a successful synthetic vascular prosthesis to facilitate recent advancements in vascular surgery.
During the many attempts made in the prior art toward the development of small diameter grafts, special attention has been given to (1) improving the biomechanical compatibility of the graft; (2) modifying the luminal surface to minimize platelet aggregation and subsequent thrombosis; and (3) pre-seeding the luminal wall with endothelial cells to provide a more natural environment to the blood component and to normalize the blood flow in the grafts.
Since Voorhees and coworkers (1952) first used Vinyon “N” cloth as a vascular graft and their conclusion that synthetic materials could serve as conduits, development in this area did not keep pace with impressive advances in materials and medical device technologies. Meanwhile, the considerable health concerns associated with vascular diseases and inadequate supply of native vessels for bypass procedures have led to the development of synthetic vascular grafts made from expanded polytetrafluoroethylene (PTFE), polyethylene terephthalate (PET) or polyurethane (PU), which satisfies the need for large size vascular grafts with patency approaching those of autologous grafts. However, the synthetic, small-diameter grafts are yet to match the autologous grafts in terms of long-term patency. For the past twenty years, no major developments have been accomplished in this area in spite of the recent rush to exploit new findings associated with tissue engineering. This may be attributed to the fundamental disconnect between highly focused areas of the academic vascular research and industrial efforts where interests broadly extend from abstract cell biology and tissue engineering to short-term, applied vascular research. It is well acknowledged that functional failures of synthetic vascular grafts are associated with (1) loss of patency due to platelet aggregation and subsequent thrombosis; (2) delayed or inadequate surface endothelialization; (3) blood leakage and/or mechanical failure due to improper graft construction and/or biomechanical properties; and (4) infection, which may be traced to compromised graft sterility. Unfortunately, in addressing these failure modes, individual investigators (1) addressed one particular mode and practically ignored others, which can affect the collective performance during in-use applications; (2) rushed to use extreme animal models in early stages of graft evaluation, which can obliterate simple findings leading to hasty interpretation of results and failure when tested in humans; and/or (3) rushed to rely heavily on tissue engineering as the solution for existing problems without acknowledging the lengthy process required to provide a prototype graft. Needless to say, a novel approach to address the issue of vascular graft failures is needed. Such an approach is expected to (1) address the different modes of graft failure in a collective manner and to provide an integrated solution to the root causes of these failures; and (2) use existing knowledge of tissue engineering in tandem with established principles of bioengineering and device design, while taking advantage of advances made in the development of transient bioabsorbable implants.